Lanosterol metabolic product(s) is involved in primordial folliculogenesis and establishment of primordial follicle pool in mouse fetal ovary.
The primordial follicles present in neonatal ovary represent the fecundity of a female throughout her reproductive life. Germ cell meiosis and apoptosis are two important events during primordial folliculogenesis. In this study, through focusing on the cytochrome P450 lanosterol 14 alphademethylase (CYP51) and its lanosterol metabolic product(s), we explored the possible regulatory mechanism of the initiation of germ cell meiosis and primordial follicle formation. The expression of CYP51 could be detected in both oocytes and granulosa cells during primordial folliculogenesis by immunochemistry. RS21745, which leads to the reduction of lanosterol metabolic product(s) level, inhibited the primordial follicle formation in a dose-dependent manner, and thus postpone the establishment of the primordial follicle pool when the mouse fetal ovaries were cultured in serum-free medium. In contrast, the number of primordial follicle increased significantly with the accumulation of the lanosterol metabolic products caused by 0.025, 0.0625, and 0.125 microM AY9944-A-7 supplements. AY9944-A-7 also up-regulated the expression of meiotic diplotene stage marker gene msy2 and primordial follicle formation regulatory gene fig-alpha. Furthermore, AY9944-A-7 decreased the expression of apoptosis gene bax and significantly prevented oocyte apoptosis from 15.37 +/- 1.97% to 3.68 +/- 0.27% (P < 0.01) in neonatal ovary in vitro. In conclusion, our results indicate that lanosterol metabolic product(s) is involved in the primordial folliculogenesis by regulating the oocyte meiosis and apoptosis.
Zhang
Hua
H
State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
Xu
Baoshan
B
Xie
Huirong
H
Zhou
Bo
B
Ouyang
Hong
H
Ning
Gang
G
Li
Ge
G
Zhang
Meijia
M
Xia
Guoliang
G
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006107:Granulosa Cells / Q000378:metabolism; D007150:Immunohistochemistry; D007810:Lanosterol / Q000378:metabolism*; D008297:Male; D008540:Meiosis; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D009867:Oogonia / Q000187:drug effects / Q000378:metabolism; D006080:Ovarian Follicle / Q000196:embryology*; D010053:Ovary / Q000196:embryology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058886:Sterol 14-Demethylase; D046509:Tissue Culture Techniques
D051792:Basic Helix-Loop-Helix Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D007810:Lanosterol; D016601:RNA-Binding Proteins; D058886:Sterol 14-Demethylase; C109920:Figla protein, mouse; C116047:Ybx2 protein, mouse; C548415:Cyp51 protein, mouse